Abstract

Human mitochondrial DNA (mtDNA) generates a highly divergent pool of alleles even within species that have dispersed
and expanded in size. On top of that codon position bias plays a relative role in prompting population wide sequence based
variations. Codon positions are immensely studied as independent evolutionary genetic markers, however co-evolution of codon
positions are still largely unexplored. Using 18,411 genome samples, we analyze nucleotide co-occurrences over mitochondrial
DNA of human sub-populations covering most of the mtDNA diversity on the earth. Our codon based network motif investigation
reveals that codon position is one of the critical factor to form higher order motifs. It is interesting to report a different evolution
of Asian genomes than those of the rest which is divulged by motifs in non-coding regions. Most notably, we demonstrate
that there are preferences of codon position co-evolution with respect to codon position sensitivity implying the selective role
of evolutionary processes on fundamental formation of genetic code in terms of codon bias evolution. These network based
findings not only recapitulates the established facts regarding the importance of each codon position in providing codon bias
but also highlight their preferential role in resulting correlated mutations. Moreover, codon based nucleotide co-occurrence
provides framework to investigate important evolutionary insights into human mitochondrial evolutionary genomics.

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